Molecular Docking to Flexible Targets

  • Jesper Sørensen
  • Özlem Demir
  • Robert V. Swift
  • Victoria A. Feher
  • Rommie E. Amaro
Part of the Methods in Molecular Biology book series (MIMB, volume 1215)


It is widely accepted that protein receptors exist as an ensemble of conformations in solution. How best to incorporate receptor flexibility into virtual screening protocols used for drug discovery remains a significant challenge. Here, stepwise methodologies are described to generate and select relevant protein conformations for virtual screening in the context of the relaxed complex scheme (RCS), to design small molecule libraries for docking, and to perform statistical analyses on the virtual screening results. Methods include equidistant spacing, RMSD-based clustering, and QR factorization protocols for ensemble generation and ROC analysis for ensemble selection.

Key words

Relaxed complex scheme Ligand filtering Protein flexibility QR factorization RMSD-based clustering ROC analysis 



This work was funded in part by through the NIH Director’s New Innovator Award Program DP2-OD007237 and the National Science Foundation’s XSEDE Supercomputer resources grant LRAC CHE060073N to R.E.A. Support from the National Biomedical Computation Resource (P41 GM103426), the Center for Theoretical Biophysics, and UCSD Drug Discovery Institute is gratefully acknowledged. J.S. thanks the Alfred Benzon Foundation for a generous postdoctoral fellowship.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jesper Sørensen
    • 1
  • Özlem Demir
    • 1
  • Robert V. Swift
    • 1
  • Victoria A. Feher
    • 1
  • Rommie E. Amaro
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of CaliforniaSan Diego, La JollaUSA

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